Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties

dc.contributor.authorCao, Yimeng
dc.contributor.authorSilverman, Lisa
dc.contributor.authorLu, Changhai
dc.contributor.authorHof, Rebecca
dc.contributor.authorWulff, Jeremy E.
dc.contributor.authorMoffitt, Matthew G.
dc.date.accessioned2021-06-27T14:45:21Z
dc.date.available2021-06-27T14:45:21Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractTwo-phase gas–liquid microfluidic reactors provide shear processing control of SN-38-loaded polymer nanoparticles (SN-38-PNPs). We prepare SN-38-PNPs from the block copolymer poly(methyl caprolactone-co-caprolactone)-block-poly(ethylene oxides) (P(MCL-co-CL)-b-PEO) using bulk and microfluidic methods and at different drug-to-polymer loading ratios and on-chip flow rates. We show that, as the microfluidic flow rate (Q) increases, encapsulation efficiency and drug loading increase and release half times increase. Slower SN-38 release is obtained at the highest Q value (Q = 400 μL/min) than is achieved using a conventional bulk preparation method. For all SN-38-PNP formulations, we find a dominant population (by number) of nanosized particles (<50 nm) along with a small number of larger aggregates (>100 nm). As Q increases, the size of aggregates decreases through a minimum and then increases, attributed to a flow-variable competition of shear-induced particle breakup and shear-induced particle coalescence. IC25 and IC50 values of the various SN-38-PNPs against MCF-7 cells show strong flow rate dependencies that mirror trends in particle size. SN-38-PNPs manufactured on-chip at intermediate flow rates show both minimum particle sizes and maximum potencies with a significantly lower IC25 value than the bulk-prepared sample. Compared to conventional bulk methods, microfluidic shear processing in two-phase reactors provides controlled manufacturing routes for optimizing and improving the properties of SN-38 nanomedicines.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipWe are grateful to the Natural Sciences and Engineering Research Council of Canada, NSERC, for financial supporten_US
dc.identifier.citationCao, Y., Silverman, L., Lu, C., Hof, R., Wulff, J. E., & Moffitt, M. G. (2019). Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties. Molecular Pharmaceutics, 16(1), 96-107. https://doi.org/10.1021/acs.molpharmaceut.8b00874.en_US
dc.identifier.urihttps://doi.org/10.1021/acs.molpharmaceut.8b00874
dc.identifier.urihttp://hdl.handle.net/1828/13072
dc.language.isoenen_US
dc.publisherMolecular Pharmaceuticsen_US
dc.subjectdrug deliveryen_US
dc.subjectmicrofluidicsen_US
dc.subjectpolymer nanoparticlesen_US
dc.subjectSN-38en_US
dc.titleMicrofluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Propertiesen_US
dc.typePostprinten_US

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Cao_Yimeng_MolPharmaceutics_2019.pdf
Size:
1.85 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2 KB
Format:
Item-specific license agreed upon to submission
Description: